The ethics of revolution in Alzheimer's research
Authors: Timothy Daly
Journal: The Lancet Healthy Longevity (2023)

Gregory and colleagues argue for a “new care pathway” based on early detection of Alzheimer's disease.1Gregory S Saunders S Ritchie CW Science disconnected: the translational gap between basic science, clinical trials, and patient care in Alzheimer's disease.Lancet Healthy Longev. 2022; 3: e797-e803Summary Full Text Full Text PDF PubMed Scopus (4) Google Scholar They assert that there is a “strong scientific and ethical impetus to shift focus to earlier disease stages to improve brain health outcomes” as part of a “brain health revolution”.1Gregory S Saunders S Ritchie CW Science disconnected: the translational gap between basic science, clinical trials, and patient care in Alzheimer's disease.Lancet Healthy Longev. 2022; 3: e797-e803Summary Full Text Full Text PDF PubMed Scopus (4) Google Scholar I agree that reducing the risk of later neurodegeneration is an imperative. However, the authors mention ethics only once in the abstract and do not cite any recent ethical scholarship. I offer an ethics perspective in this Correspondence to provide balance to their call for a brain health revolution by warning against the harms of the over-medicalisation of biomarkers of Alzheimer's disease pathology. The authors' concern that the historical focus on the clinical syndrome of dementia still dominates research is unfounded. Alzheimer's disease as a historical clinicopathological entity has been “reconceptualised” to a biological continuum with major repercussions for research and the clinic.2Schermer MHN Richard E On the reconceptualization of Alzheimer's disease.Bioethics. 2019; 33: 138-145Crossref PubMed Scopus (35) Google Scholar The authors mention blood-based biomarkers as one important innovation. Over 135 papers have been indexed on PubMed on blood-based biomarkers in Alzheimer's disease in 2022 alone, which are “already transforming both symptomatic and preventative Alzheimer's disease clinical trials ... [at a] furious pace”.3Tariot P Editorial: blood-based biomarkers for Alzheimer's disease: are we there yet?.J Prev Alzheimers Dis. 2022; 9: 565-566PubMed Google Scholar Thus, the revolution of the Alzheimer's disease continuum is already well under way. This reconceptualisation of Alzheimer's disease is fraught with ethical issues. It is still not known which individuals with biomarkers of Alzheimer's disease pathology will develop sporadic Alzheimer's disease; if they do, there is no fully approved treatment for them, and furthermore, the popular understanding of Alzheimer's disease is still based on the historical clinicopathological entity and thus lagging behind expert understanding of the Alzheimer's disease continuum. This situation means that, if the research community exaggerates the therapeutic and prognostic value of Alzheimer's disease pathology, they will create conflict between the interests of individuals and the interests of research.2Schermer MHN Richard E On the reconceptualization of Alzheimer's disease.Bioethics. 2019; 33: 138-145Crossref PubMed Scopus (35) Google Scholar The authors raise an interesting point when they criticise “decades of repeating the same clinical trial methodologies”.1Gregory S Saunders S Ritchie CW Science disconnected: the translational gap between basic science, clinical trials, and patient care in Alzheimer's disease.Lancet Healthy Longev. 2022; 3: e797-e803Summary Full Text Full Text PDF PubMed Scopus (4) Google Scholar However, instead of method, it is arguable that the ethical problem facing such trials is over-reliance on lowering amyloid in individuals with biomarkers for Alzheimer's disease pathology.4Daly T Herrup K Espay AJ An ethical argument for ending human trials of amyloid-lowering therapies in Alzheimer's disease.AJOB Neurosci. 2022; (published online Oct 5.)https://doi.org/10.1080/21507740.2022.2129858Crossref Scopus (3) Google Scholar Although the authors’ call for personalised medicine is a worthy ultimate goal, there is ample scope for a logical first step of “rescue medicine” based on approaches other than amyloid-lowering.5Espay AJ Sturchio A Schneider LS Ezzat K Soluble amyloid-β consumption in Alzheimer's disease.J Alzheimers Dis. 2021; 82: 1403-1415Crossref Scopus (21) Google Scholar Once clinically significant improvements on the Alzheimer's disease continuum are established, it will be possible to “stratify patients for etiology-specific treatments and launch precision medicine for Alzheimer's disease”.5Espay AJ Sturchio A Schneider LS Ezzat K Soluble amyloid-β consumption in Alzheimer's disease.J Alzheimers Dis. 2021; 82: 1403-1415Crossref Scopus (21) Google Scholar I declare no competing interests. Science disconnected: the translational gap between basic science, clinical trials, and patient care in Alzheimer's diseaseBoth research and clinical practice have traditionally centred on the dementia syndrome of Alzheimer's disease rather than its preclinical and prodromal stages. However, there is a strong scientific and ethical impetus to shift focus to earlier disease stages to improve brain health outcomes and help to keep affected individuals symptom-free (dementia-free) for as long as possible. We provide an overview of recent advancements in early detection, drug development, and trial methodology that should be utilised in the development of new therapies for use in brain health clinics. Full-Text PDF Open Access